Bargellini, T

Batignani, Giacomo

Nesi, Gabriella

Scaringi, S

Tonelli, F.

English

Florence Research

Abstract. Gallbladder carcinoma is a rare, but often lethaldisease. Unfortunately, at the time of diagnosis, patientsusually have advanced disease (T3-T4) and long-termsurvival is dismal, ranging from 5 to 12% in the literature.However, this cancer can be successfully treated when thetumour is organ-confined (T1-T2 tumours), as happens in thecase of incidental diagnosis at the time of cholecystectomyfor gallstones. Here we describe a patient with recurrentgallbladder carcinoma who, treated with iterative surgicalresection, is alive and disease-free at 5 years after the finalsurgical procedure.Gallbladder carcinoma is a rare, but often lethal disease. Itrepresents the fifth most common gastrointestinalmalignancy and the most common biliary tract cancer.Considering the ineffectiveness of chemotherapy andradiotherapy as first-line treatment, surgery remains the onlychance for cure. Unfortunately, at the time of diagnosis,patients usually have advanced disease (T3-T4) and, despitetechnological improvements in hepato-biliary surgery, only15-47% are candidates for resection (1-3). Overall long-termsurvival is dismal, ranging from 5 to 12% in the literature(4). However, this cancer can be successfully treated whenthe tumour is organ-confined (T1-T2 tumours), as happensin the case of incidental diagnosis at the time ofcholecystectomy for gallstones. Conversely, when recurrencetakes place, prognosis is very poor, and no survival beyond 5years is reported (5).We describe the case of a patient affected with recurrentgallbladder carcinoma who, treated with iterative surgicalresection, is alive and disease-free at 5 years after the finalsurgical procedure.Case ReportA 73-year-old woman presented in October 2001 withabdominal pain. For 3 months she had been suffering fromsteady pain, episodically acute, located in the upper rightabdominal quadrant, which gradually subsided after a fewhours. It was associated with vomiting, but with no fever orjaundice. She did not complain of loss of appetite or weight, norchanges in bowel habits. Her past history was unremarkable.On physical examination, the abdomen was tender topalpation in the epigastric and upper right quadrant.Murphy’s sign was negative. The leukocyte count, serumbilirubin, alkaline phosphatase and amylase were withinnormal values. Sonography showed multiple gallstoneswithout thickening of the gallbladder wall or dilatation of thecommon bile duct. One week later, elective laparoscopiccholecystectomy was carried out. The gallbladder was notopened during the procedure, but extracted through anendobag. No frozen sections were performed. Pathologicalexamination revealed the presence of a polypoid tumour of 2cm in diameter, located in the fundus of the gallbladder,corresponding to a poorly differentiated adenocarcinomainfiltrating the muscle layer (pT2/Nx/Mx) (Figure 1A).Liver resection of the gallbladder bed and lymph nodedissection of the hepatic pedicle was proposed but the patientrefused, accepting, however, adjuvant chemotherapy withfluorouracil and leucovorin, according to the de Gramontschedule (6). This was interrupted after 4 cycles becauseherpes zoster had occurred. The patient was followed upevery six months with clinical examination, CT scan andbiological markers. In October 2002, CT showed a single 4-cm lesion in the inferior splenic pole, suggestive ofmetastasis (Figure 2-A). Biological markers were in thenormal range. The patient underwent splenectomy and lymphnode dissection of the hepatic pedicle. The postoperativecourse was uneventful; pathology revealed metastasis ofpoorly differentiated adenocarcinoma matching the primarytumour of the gallbladder (Figure 2B). Lymph nodes of thehepatic pedicle were free of disease. No further adjuvanttreatment was administered.215Correspondence to: Stefano Scaringi, MD, University of FlorenceCareggi University Hospital, Italy. e-mail: stefano.scaringi@unifi.it Key Words: Gallbladder carcinoma, metachronous metastasis, long-term survival. in vivo 24: 215-218 (2010)Iterative Surgical Resection of a Recurrent Gallbladder Carcinoma with Long-term Survival: Report of a CaseSTEFANO SCARINGI, GABRIELLA NESI, TATIANA BARGELLINI, GIACOMO BATIGNANI and FRANCESCO TONELLIUniversity of Florence Careggi University Hospital, Italy0258-851X/2010 $2.00+.40in vivo 24: 215-218 (2010)216Figure 3. A: CT scan showing the recurrence involving the pancreatic tail and the greater curvature of the stomach (white arrow); B: poorlydifferentiated adenocarcinoma infiltrating the external layer of the gastric wall.Figure 2. A: CT scan showing the metastasis at the inferior splenic pole (white arrow); B: parenchymal intravascular emboli with integrity of thesplenic capsule.Figure 1. A: Poorly differentiated adenocarcinoma infiltrating the muscle layer; B: intense immunoreactivity with cytokeratin-7; C-D: markers ofneuroendocrine tumours, chromogranin and synaptophysin, are negative.In March 2003, a CT scan showed a solitary lesion of 2.5 cmin diameter involving the pancreatic tail and the greatercurvature of the stomach, indicative of recurrence (Figure 3A).The patient was then subjected to distal pancreatectomy en-blocwith sleeve gastrectomy and omentectomy. Portal-sites were notexcised. Pathology confirmed metastasis of poorly differentiatedadenocarcinoma infiltrating the external layer of the gastric wall(Figure 3B). Five years later the patient is alive withoutevidence of recurrence.Discussion Long-term survival of a patient with metachronousmetastasis of primary gallbladder carcinoma is an uncommonevent, never previously reported in the literature.Gallbladder carcinoma is a tumour with an aggressivebiological behaviour and poor prognosis. Patients are oftendiagnosed at advanced stage and surgical resection is theonly possibility of cure, with survival rates ranging from 5%to 12% at 5 years (4, 7). Nevertheless, a different assessmentshould be made for tumours diagnosed incidentally afterlaparoscopic cholecystectomy. They often present at an earlystage (T1/T2) with a 5-year survival of 85% for T1 tumoursoperated with simple cholecystectomy, and 61% for T2tumours, if promptly re-operated and liver resectionperformed (usually segments IVb-V), along with lymph nodedissection of the hepatic pedicle (8, 9). Notably, the presenceof nodal metastasis at this site is the most important factorto influence survival, as reported by Lin et al. (9). Moreover,a recent review described how the presence of residualdisease and the ability to achieve R0 represent significantprognostic factors (10).In the current case, pathology revealed a T2 primarytumour, while the nodal dissection of the hepatic pedicle,performed at the time of the second operation, gave noevidence of metastasis. We hypothesise that these featuresinfluenced the patient’s outcome positively. It is worthemphasising that the splenic recurrence was a true vascularmetastasis rather than a peritoneal implantation, as proven bythe presence of parenchymal intravascular emboli and theintegrity of the splenic capsule. However, the physio-pathological mechanisms of tumour vascular spread to thespleen, in the absence of portal hypertension, still remainunclear. Indeed, no report has been found in the literatureconcerning splenic metastasis from T2 gallbladder carcinomas. On histological examination, poorly differentiatedcarcinomas of the gallbladder may exhibit various growthpatterns. In some instances, neoplastic cells form cords andnests, or they infiltrate simply as individual cells. A diffusesheet-like component may be seen, as in our case.Immunohistochemically, stains for cytokeratin 7 (Figure 1B),and carcino-embryonic antigen show intense immunoreactivityin a dominant population of tumour cells. Several mucin-related glycoproteins, such as MUC1 and MUC5AC, are alsonormally expressed, although they may be focal, while generalmarkers of neuroendocrine differentiation, such as neuron-specific enolase (NSE), chromogranins and synaptophysin, areinvariably negative (Figure 1-C,D).As regards treatment of gallbladder carcinoma, it iscommon opinion that adjuvant therapy plays a marginal role.In a recent review, chemotherapy was considered onlypalliative in non-resectable or metastatic tumours, and theauthors concluded that no single or combined regimensshould be recommended as a standard of care (5).This report suggests that surgical resection of solitarymetachronous metastasis should not be excluded astherapeutic approach, even for gallbladder carcinoma, whichshould not represent a predetermined condition in case oforgan confined tumours (T1-T2).References1 Bartlett DL, Fong Y, Fortner JG, Brennan MF and Blumgart LH:Long-term results after resection for gallbladder cancer.Implications for staging and management. Ann Surg 224(5):639-646, 1996.2 Benoist S, Panis Y and Fagniez PL: Long-term results aftercurative resection for carcinoma of the gallbladder. FrenchUniversity Association for Surgical Research. Am J Surg 175(2):118-122, 1998.3 Fong Y, Jarnagin W and Blumgart LH: Gallbladder cancer:comparison of patients presenting initially for definitiveoperation with those presenting after prior noncurativeintervention. Ann Surg 232(4): 557-569, 2000.4 Cubertafond P, Gainant A and Cucchiaro G: Surgical treatmentof 724 carcinomas of the gallbladder. Results of the FrenchSurgical Association Survey. Ann Surg 219(3): 275-280, 1994.5 Verslype C, Prenen H and Van CE: The role of chemotherapy inbiliary tract carcinoma. HPB (Oxford) 10(3): 164-167, 2008.6 de GA, Bosset JF, Milan C, Rougier P, Bouche O, Etienne PL etal: Randomized trial comparing monthly low-dose leucovorinand fluorouracil bolus with bimonthly high-dose leucovorin andfluorouracil bolus plus continuous infusion for advancedcolorectal cancer: a French intergroup study. J Clin Oncol 15(2):808-815, 1997.7 Wilkinson DS: Carcinoma of the gall-bladder: an experience andreview of the literature. Aust N Z J Surg 65(10): 724-727, 1995.8 Kondo S, Takada T, Miyazaki M, Miyakawa S, Tsukada K,Nagino M et al: Guidelines for the management of biliary tractand ampullary carcinomas: surgical treatment. J HepatobiliaryPancreat Surg 15(1): 41-54, 2008.9 Lin HT, Liu GJ, Wu D and Lou JY: Metastasis of primarygallbladder carcinoma in lymph node and liver. World JGastroenterol 11(5): 748-751, 2005.10 Pilgrim C, Usatoff V and Evans PM: A review of the surgicalstrategies for the management of gallbladder carcinoma basedon T stage and growth type of the tumour. Eur J Surg Oncol35(9): 903-907, 2009.Received January 19, 2010Accepted February 3, 2010Scaringi et al: Surgical Treatment of Recurrent Gallbladder Carcinoma217

Iterative surgical resection of a recurrent gallbladder carcinoma with long-term survival: report of a case.

https://flore.unifi.it/bitstream/2158/632685/1/PDF%20IN%20VIVO%20marzo%20aprile%202010%20nps1C.pdf

Iterative surgical resection of a recurrent gallbladder carcinoma with long-term survival: report of a case.

Abstract

Similar works

Full text

Available Versions

Florence Research